SGCD

sarcoglycan delta

Basic information

Region (hg38): 5:155870344-156767788

Links

ENSG00000170624 ∙ NCBI:6444 ∙ OMIM:601411 ∙ HGNC:10807 ∙ Uniprot:Q92629 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive limb-girdle muscular dystrophy type 2F (Definitive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2F (Moderate), mode of inheritance: AR
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• autosomal recessive limb-girdle muscular dystrophy type 2F (Supportive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2F (Strong), mode of inheritance: AR
• dilated cardiomyopathy 1L (Disputed Evidence), mode of inheritance: AD
• autosomal recessive limb-girdle muscular dystrophy (Definitive), mode of inheritance: AR
• dilated cardiomyopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1L	AR	Cardiovascular	The condition can include severe cardiac manifestations, and knowledge may allow surveillance (eg, with EKG, echocardiogram, and Holter monitoring) and early medical management, which may ameliorate morbidity and mortality; Heart transplantation may be indicated in individuals with severe dilated cardiomyopathy	Cardiovascular; Musculoskeletal	8841194; 8776597; 10735275; 9832045; 10069710; 10974018,; 18285821; 19259135
Digenic inheritance (with SGCB) has been suggested, but the evidence is unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SGCD gene.

• Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2F (443 variants)
• not_provided (140 variants)
• Dilated_cardiomyopathy_1L (124 variants)
• Inborn_genetic_diseases (104 variants)
• not_specified (60 variants)
• Qualitative_or_quantitative_defects_of_delta-sarcoglycan (20 variants)
• SGCD-related_disorder (17 variants)
• Cardiomyopathy (11 variants)
• Limb-girdle_muscular_dystrophy,_recessive (10 variants)
• Autosomal_recessive_limb-girdle_muscular_dystrophy (6 variants)
• Primary_dilated_cardiomyopathy (5 variants)
• Abnormality_of_the_musculature (2 variants)
• Neuromuscular_disease (2 variants)
• Dilated_cardiomyopathy_1A (1 variants)
• Dilated_Cardiomyopathy,_Dominant (1 variants)
• MUSCULAR_DYSTROPHY,_LIMB-GIRDLE,_AUTOSOMAL_RECESSIVE_6,_DIGENIC (1 variants)
• Muscular_dystrophy (1 variants)
• Hypertrophic_cardiomyopathy_1 (1 variants)
• Primary_familial_dilated_cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SGCD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000337.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	123		126
missense	1	3	175	6	1	186
nonsense	9	3	4			16
start loss			1			1
frameshift	12	11	1			24
splice donor/acceptor (+/-2bp)	1	11	8	1		21
Total	23	28	192	130	1

Highest pathogenic variant AF is 0.000022561024

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SGCD	protein_coding	protein_coding	ENST00000337851	8	897446

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00207	0.980	124625	0	12	124637	0.0000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.195	144	151	0.955	0.00000775	1842
Missense in Polyphen		44	50.692	0.86799		641
Synonymous	-0.181	61	59.2	1.03	0.00000318	580
Loss of Function	2.08	7	15.9	0.439	9.44e-7	187

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000194	0.000194
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000467	0.0000464
European (Non-Finnish)	0.0000628	0.0000619
Middle Eastern	0.00	0.00
South Asian	0.0000353	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
• Disease: DISEASE: Limb-girdle muscular dystrophy 2F (LGMD2F) [MIM:601287]: An autosomal recessive degenerative myopathy initially affecting the proximal limb girdle musculature. Muscle from patients shows a complete loss of delta-sarcoglycan as well as of the others components of the sarcoglycan complex. {ECO:0000269|PubMed:9832045}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1L (CMD1L) [MIM:606685]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:10974018}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Dilated cardiomyopathy (DCM) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy (Consensus)

Recessive Scores

• pRec: 0.368

Intolerance Scores

• loftool: 0.276
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• pHI: 0.150
• hipred: Y
• hipred_score: 0.668
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.789

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sgcd
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: sgcd
• Affected structure: ventricular myocardium
• Phenotype tag: abnormal
• Phenotype quality: decreased contractility

Gene ontology

• Biological process: muscle organ development;cell death;calcium-mediated signaling;cellular protein-containing complex localization;cardiac muscle tissue development;cardiac muscle fiber development;calcium ion homeostasis;heart contraction;coronary vasculature morphogenesis;cardiac muscle cell contraction
• Cellular component: cytoskeleton;plasma membrane;dystrophin-associated glycoprotein complex;sarcoglycan complex;integral component of membrane;sarcoplasmic reticulum;sarcolemma